The immunopathology of Alzheimer's disease and some related disorders

Current evidence clearly indicates that elements of the immune system are involved in the pathogenesis of the principal lesions characterizing Alzheimer's disease (AD). Findings are in accord with features associated with both the innate and adaptive immune mechanisms involved in a predominantly local inflammatory response within the parenchyma. Many of the features are unique to AD, presumably related to the unusual properties of beta amyloid protein. Remarkably, the brain holds the capacity to produce almost all the immune system mediators which largely seem to be generated by glia comprising both astrocytes and microglia. While a variety of humoral mediators including classical acute phase proteins (and serpins) are increased and released, the complement seems most intrinsically involved. The cellular response is elaborated by microglia which seem the main immunocompetent cells partaking in the response. These appear to function as pluripotent macrophages expressing both classes of MHC antigens. Further characterization of this interesting response to cerebral amyloidosis will be challenging.